The overall objective of the project is to investigate the structure and biosynthesis of human serum alpha-1-antitrypsin, the deficiency of which is associated with pediatric cirrhosis and pulmonary emphysema. Cyanogen bromide cleavage of M, S, and Z-variants of alpha-1-antitrypsin will provide 4 oligopeptides that will be used in a sialyl-transferase assay containing human liver sialytransferase. These oligopeptides will be modified chemically by specific amino acid reagents and by proteases such as pronase, trypsin, chymotrypsin and dipeptidase in order to determine the extent to which the polypeptide component influences the attachment of sialic acid residues. In addition, the human liver sialytransferase will be purified to homogeneity and characterized with regard to chemical, physical and kinetic properties. Finally, the structure of the oligosaccharide moieties of alpha-1-antitrypin will be determined. These studies will: (1) establish the structure of an important serum glycoprotein implicated in human disease, (2) contribute to our understanding of the role of carbohydrate residues in glycoprotein synthesis and secretion, and (3) possibly lead to the recognition of improved therapeutic and diagnostic procedures. BIBLIOGRAPHIC REFERENCES: Miller, R.R., Kuhlenschmidt, M.S., Coffee, C.J., Kuo, I. and Glew, R.H. "Comparison of the Chemical, Physical and Survival Properties of Normal and Z-Variant Alpha-1-Antitrypsins", J. Biol. Chem., 251, 4751-4757 (1976). Miller, R.R., Peters, S.P., Kuhlenschmidt, M.S., and Glew, R.H. "The Use of Ion-Exchange Resins in the Application of Protein Samples to Gel Filtration Columns", Anal. Biochem., 72. 45-48 (1976).